Among numerous other factors, oxidation of low-density lipoproteins (LDL) is frequently associated with arterial plaque build-up, which eventually may result in significant obstruction of a blood vessel and/or provide a source of material that can block downstream vasculature (see e.g., Biochem Soc Trans., 2001, 29, 358-362). Therefore, oxLDL has recently been proposed as a potential prognostic marker of cardiovascular conditions (see e.g., Meisinger et al., Circulation, 2005, 112, 651-657).
Use of antioxidants, and especially dietary antioxidants to prevent LDL oxidation appears to present an attractive alternative to pharmaceutical and/or interventional therapy. For example, polyphenols, tocopherol, and ascorbic acid were described as effective agents to reduce LDL-oxidation (see e.g., Eur J Pharmacol. 2005 Apr. 25; 513(3): 173-9), as well as gentisic acid, an aspirin metabolite, as described elsewhere (Eur J Pharmacol. 2005 Apr. 25; 513(3): 173-9). Isoflavones were reported as being at least somewhat effective as described in Am J Clin Nutr. 2005 January; 81(1):43-9. However, most of the isolated compounds available as over-the-counter compositions have one or more problems. For example, high-dose tocopherol administration has been reported as increasing the risk for certain neoplasms. Long-term administration of aspirin is typically associated with an increased risk of intestinal bleeding, and polyphenols, especially where administered in liquid oral formulation, tend to stain teeth, and isoflavones may exhibit estrogenic effects, especially at relatively high dosages. Moreover, initial and hopeful reports regarding the beneficial role of antioxidant vitamins against atherosclerosis were followed by the negative results of almost all large randomized trials (see e.g., Am J Physiol Heart Circ Physiol 282: H797-H802, 2002).
Therefore, it has been concluded that treatment with the antioxidant vitamins C and E is not recommended for prevention or treatment of coronary atherosclerosis dietary (see e.g., Herz, 2003, 28: 628-638).
In further known methods to reduce LDL oxidation, certain functional food products and supplements were described as reducing LDL oxidation at least to some degree. For example, selected pomegranate (see e.g., J Nat Prod., 2004, 67, 2096-8), almond (see e.g., Circulation, 2002, 106, 1327-32), and grape (see e.g., Free Radical Res., 2003, 37, 573-84) preparations were reported to have an effect of LDL oxidation. While such methods appear to hold at least some promise, availability, preparation, and economic factors associated with such materials often precluded successful marketing of these products and supplements. Moreover, the protective effect of these known preparations was at least in some cases less than desirable.
Therefore, while numerous compositions and methods are known in the art to reduce LDL oxidation, all or almost all of them suffer from one or more disadvantages. Thus, there is still a need to provide improved compositions and methods that reduce LDL oxidation, and most advantageously compositions and methods that also increase HDL levels.